The COBRE Program in the "Molecular Mechanisms and Genetics of Autoimmunity" at the Oklahoma Medical Research Foundation (OMRF) has sponsored 14 studies, generated >240,000,000 genotypes, published 130 important manuscripts, made possible the funding of multiple NIH grants, and has resulted in recruiting of 8 new faculty members (Susan Kovats, PhD, Amr Sawaiha, MD, Mary Beth Humphrey, MD, PhD, Kathy Moser, PhD, Pat Gaffney, MD, Jonathan Wren, PhD, Courtney Gray-McGuire, PhD, and Marta Alarcon-Riquelme, MD, PhD). All in all, we have met the standard for success. Our mantra is professional growth through mentoring and through building relevant infrastructure. Several of our junior scientists have done well. For example, Swapan K. Nath, PhD, identified ITGAM (aka CD11b, MAC-1, CR3) as a gene for systemic lupus erythematosus and R77H as its probable causative polymorphism. His essential findings have been confirmed in multiple other studies. Swapan Nath, Mary Beth Humphrey, MD, PhD, Amr Sawaiha, MD, Susan Kovats, PhD, and Ken Kaufman, PhD have been funded respectively, by an R01, another R01 an R03, an R21, and a VA Merit Award. With its emphasis on mentoring our COBRE Program has changed our scientific culture toward open, mutual encouragement of faculty, whether senior or junior. This has also served to develop careers in science and to produce outstanding scientific results. To begin the coming five years we present 4 research projects, a recruiting study and one pilot study. Each COBRE scientist funded holds the potential promise for an independent career, producing critical insights and experiments. Scientifically, they will be supported by Nucleic Acid and Data Analysis Cores with mentoring and other functions under an Administrative Core. In addition, the recruiting successes will be continued with a Recruiting Core designed to provide adjunct support to the expansion underway at the OMRF. With the competitive renewal, our plan is to build as many productive scientific careers as possible, to populate our institutions with as many exceptional faculty members as possible, to enhance our international reputation for scientific excellence in autoimmunity, and to produce critically important new discoveries in the process. PUBLIC HEALTH RELEVANCE (provided by applicant): Autoimmune diseases are estimated to afflict as many as 50,000,000 of our fellow citizens. This COBRE Program will study process, identify genes, and develop knowledge basic to understanding these disorders, concentrating on systemic lupus erythematosus, a potentially deadly autoimmune disease, found mainly in young women, so that the new knowledge will lead to new diagnostics, prognostics and therapeutics.